The invention generally relates to the area of mass spectroscopic analysis, and more particularly is concerned with method and apparatus, including multi-reflecting time-of-flight mass spectrometer (MR-TOF MS) and with the apparatus and method of improving the duty cycle of the orthogonal injection at a low repetition rate.
Time-of-flight mass spectrometers (TOF MS) are increasingly popular, both as stand-alone instruments and as a part of mass spectrometry tandems like a Q-TOF or a TOF-TOF. They provide a unique combination of high speed, sensitivity, resolving power (resolution) and mass accuracy. Recently introduced multi-reflecting time-of-flight (MR-TOF) mass spectrometers demonstrated a substantial raise of resolution above 105 (See the publication entitled “Multi-Turn Time-of-Flight Mass Spectrometers with Electrostatic Sectors” by Michisato Toyoda, Daisuke Okumura, Morio Ishihara and Itsu Katakuse, published in J. Mass Spectrom. 38 (2003) pp. 1125-1142, and the publication by Verentchikov et al. published in the Russian Journal of Technical Physics (JTP) in 2005 vol. 50, No. 1, pp. 76-88).
In a co-pending international PCT patent application by the inventors (WO 2005/001878 A2), the entire disclosure of which is incorporated herein by the reference, there was suggested an MR-TOF with planar geometry and a set of periodic focusing lenses. The multi-reflecting scheme provides a substantial extension of the flight path and thus improves resolution, while the planar (substantially 2-D) geometry allows the retention of full mass range. Periodic lenses located in a field-free space of the MR-TOF provide a stable confinement of ion motion along the main jig-saw trajectory. To couple the MR-TOF to continuous ion beams, gas-filled radio frequency (RF) ion traps were proposed to accumulate ions in between sparse pulses of the MR-TOF.
However, as shown in an ASMS presentation (Abstracts of ASMS 2005 and ASMS 2006 by B. N. Kozlov et. al.), an ion trap source introduces at least two significant problems: 1) ion scattering on gas; and 2) space charge effects on ion beam parameters. Those factors limit an ion current, which could be converted into ion pulses. Experiments with storing ions near the exit of an RF ion guide show that ionic space charge starts affecting parameters of ejected ions when the number of stored ions exceeds N=30,000. Similar estimates have been obtained in the literature for linear ion traps and 3-D (Paul) traps. Gas scattering requires operation at a gas pressure below 1 mtorr which, in turn, requires dampening time in the order of T=10 ms, i.e., limiting pulsing repetition rate by F=100 Hz (Abstracts of ASMS 2005 and ASMS 2006 by B. N. Kozlov et. al.). All together it means that an ion flux above N*F=3,000,000 ions/s (corresponding to a current I=0.5 pA) will be affecting the turnaround time and the energy spread of ejected ions. This current is at least a factor of 30 lower compared to the intensity of modem ion sources, like ESI and APCI. If no measures are taken, the resolution and mass accuracy of the TOF MS would depend on ion beam intensity and, thus, on parameters of the analyzed sample. For tandems with chromatography like a liquid chromatographic mass spectrometer (LC-MS) and a liquid chromatographic tandem mass spectrometer (LC-MS-MS), it would mean that mass scale would be shifted at a time of elution of chromatographic peaks. An automatic adjustment of peak intensity would stabilize mass scale, but will introduce additional ion losses and limit a duty cycle of the trap (efficiency of converting continuous ion beams into ion pulses) to several percent.
The use of a linear ion trap instead of a three-dimensional ion trap (see U.S. Pat. No. 5,763,878 by J. Franzen) would reduce space charge effects. The linear trap is known to produce ion bunches with up to 106 ions per bunch (LTQ-FTMS). The solution still has drawbacks related to ion scattering on gas, slow pulsing and, as a result, a large load on the detector and the data acquisition system, currently known to have a limited dynamic range.
A method of orthogonal pulsed acceleration is widely used in time-of-flight mass spectrometry (oa-TOF MS). It allows converting a continuous ion beam into ion pulses with a very short time spread down to 1 ns. Because of operating with a low diverging ion beam, a so-called turnaround time drops substantially. Due to a high frequency of pulses (10 kHz) and because of an elongated ion beam, the efficiency of the conversion (so-called duty cycle) in a conventional oa-TOF is quite acceptable while space charge problems are avoided. In a singularly reflecting TOF (a so-called “reflectron”) the duty cycle of the orthogonal accelerator is known to be in the order of K=10-30% for ions with highest m/z in the spectrum (dropping proportional to the square root of m/z for other ions).
Unfortunately, the conventional orthogonal acceleration scheme is poorly applicable to MR-TOF because of two reasons:                a) longer flight times (1 ms) and lower repetition rate would reduce the duty cycle by more than an order of magnitude; and        b) a smaller acceptance of the analyzer to ion packet width in the drift direction would require a short length of ion packet limited by the aperture of periodic focusing lenses (this length is estimated to be below 5-7 mm) which would limit duty cycle again.        
The overall expected duty cycle of an MR-TOF with a conventional orthogonal accelerator is under 1 percent.
The duty cycle of an orthogonal accelerator can be improved in a so-called “pulsar” scheme (such as that disclosed in U.S. Pat. No. 6,020,586 by T. Dresch) at the cost of reducing mass range. The scheme suggests trapping ions in a linear ion guide and releasing ions periodically. Orthogonal accelerator is synchronized to release pulses. The scheme also introduces a significant energy spread in the direction of continuous ion beam. The benefit of the scheme is marginal, even in case of prolonged flight times.
The mass range in a “pulsar” scheme can be extended by application of a time-dependent electrostatic field, which bunches ions of different masses at the position of the orthogonal accelerator (see, for example, U.S. Patent Application Publication No. US 2004/0232327 A1). This solution, however, is not suitable for ion injection into an MR-TOF MS because ions of different masses gain different energies during bunching and thus are orthogonally accelerated under essentially different angles with respect to the direction of the continuous ion beam. Such a large angular spread cannot be accepted by the MR-TOF MS.
Summarizing the above, a planar multi-reflecting analyzer significantly improves resolving power while providing a full mass range. However, ion sources of the prior art do not provide a sufficient duty cycle above several percent, or suffer other drawbacks. Accordingly, there is a need for instrumentation simultaneously providing high resolution and an efficient conversion of ion flux into ion pulses.